The synthesis of novel radiopharmaceuticals is facilitated by the ability to react the same radiolabeled molecule with a number of biologically active substrates. High molecular weight proteins including human serum albumin, human serum fibrinogen, and immunoglobulin A have previously been radiolabeled using p-(18F)fluorophenacyl bromide[(18F)FPB]. The exact site of the attachment of the [(18F)FPB] has been reported involving the use of solid phase bromination technique. Results obtained during attempts to label octreotide, an eight amino acid analog of the naturally occuring peptide somatostatin, prompted the current work. The p-(18F)fluorophenacyl bromide was expected to react readily with the N-terminal amine of octreotide. However, HPLC analysis of the reaction mixture showed no reaction between (18F)FPB, but decomposition of the FPB was observed. The functional groups available for reaction on protected octreotide are the N-terminal amine and the hydroxyl groups of threonine and threoninol. In summary, we have evaluated the relative reactivity of (18F)FPB with a variety of nucleophiles. We have demonstrated the (18F)FPB has a dramatic preference for a thiol as opposed to any other nucleophilic moiety. This research will be applied to small peptides in an effort to fully understand which amino acid residues are conducive to labeling with (18F)FPB.